Rapid SARS-CoV-2 Seroprevalence Survey in Central and Western Divisions of Fiji, 2021.

During November-December 2021, we performed a SARS-CoV-2 seroprevalence survey in Central and Western Divisions of Fiji. A total of 539 participants 8-70 years of age were 95.5% (95% CI 93.4%-97.1%) seropositive, indicating high community levels of immunity. Seroprevalence studies can inform public health responses to emerging SARS-CoV-2 variants.

Prevalence and incidence of emergency department presentations and hospital separations with injecting-related infections in a longitudinal cohort of people who inject drugs.

People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31-36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25-30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.

Repaired coarctation of the aorta, persistent arterial hypertension and the selfish brain.

BACKGROUND: It has been estimated that 20-30% of repaired aortic coarctation (CoA) patients develop hypertension, with significant cardiovascular morbidity and mortality. Vertebral artery hypoplasia (VAH) with an incomplete posterior circle of Willis (ipCoW; VAH + ipCoW) is associated with increased cerebrovascular resistance before the onset of increased sympathetic nerve activity in borderline hypertensive humans, suggesting brainstem hypoperfusion may evoke hypertension to maintain cerebral blood flow: the "selfish brain" hypothesis. We now assess the "selfish brain" in hypertension post-CoA repair. METHODS: Time-of-flight cardiovascular magnetic resonance angiography from 127 repaired CoA patients (34 ± 14 years, 61% male, systolic blood pressure (SBP) 138 ± 19 mmHg, diastolic blood pressure (DBP) 76 ± 11 mmHg) was compared with 33 normotensive controls (42 ± 14 years, 48% male, SBP 124 ± 10 mmHg, DBP 76 ± 8 mmHg). VAH was defined as < 2 mm and ipCoW as hypoplasia of one or both posterior communicating arteries. RESULTS: VAH + ipCoW was more prevalent in repaired CoA than controls (odds ratio: 5.8 [1.6-20.8], p = 0.007), after controlling for age, sex and body mass index (BMI). VAH + ipCoW was an independent predictor of hypertension (odds ratio: 2.5 [1.2-5.2], p = 0.017), after controlling for age, gender and BMI. Repaired CoA subjects with VAH + ipCoW were more likely to have difficult to treat hypertension (odds ratio: 3.3 [1.01-10.7], p = 0.049). Neither age at time of CoA repair nor any specific repair type were significant predictors of VAH + ipCoW in univariate regression analysis. CONCLUSIONS: VAH + ipCoW predicts arterial hypertension and difficult to treat hypertension in repaired CoA. It is unrelated to age at time of repair or repair type. CoA appears to be a marker of wider congenital cerebrovascular problems. Understanding the "selfish brain" in post-CoA repair may help guide management. JOURNAL SUBJECT CODES: High Blood Pressure; Hypertension; Magnetic Resonance Imaging (MRI); Cardiovascular Surgery; Cerebrovascular Malformations.

Success in a Fontan pregnancy: how important is ventricular function?

The Fontan operation is a palliative surgical procedure for patients whose hearts cannot support a biventricular circulation. The haemodynamic changes that occur in pregnancy are particularly challenging for Fontan patients and the outcomes are variable. We present a case where fetal outcome was particularly poor despite a lack of high risk features pre-pregnancy.

Strengthening and implementing health technology assessment and the decision-making process in the Region of the Americas.

OBJECTIVE: Health technology assessment (HTA) has been adopted by countries in order to improve allocative efficiency in their health systems. This study aimed to describe and analyze the HTA decision-making process in the Region of the Americas. METHODS: A literature review was done to better understand the HTA situation in the Region. Also, in 2014 and 2015, individuals responsible for conducting HTA in countries of the Americas were identified and received a questionnaire on HTA and the decision-making process. RESULTS: A total of 46 questionnaire responses were obtained, from 30 countries. The respondents were similar in terms of their institutions, main funding sources, and technology types assessed. Of the 46 respondents, 23 (50%) work for their respective ministry of health. Also, 36 (78%) undertake and/or coordinate HTA through coverage and reimbursement/pricing decisions and other HTA-related activities, while 24 (52%) use HTA for emerging technologies. While some countries in the Region have created formal HTA units, there is a weak link between the HTA process and decision-making. Most of the countries with recognized HTA institutions are members of the Health Technology Assessment Network of the Americas (RedETSA). Despite the advances in the Region overall, most countries in Central America and the Caribbean are still at the early stages of implementing HTA to support decision-making. CONCLUSIONS: Many countries in the Americas have benefited from the exchange and capacity-building opportunities within RedETSA. However, there are still many challenges to overcome in the Region in terms of the discussion and creation of HTA-related policies.

Resistance to first-line antibiotic therapy among patients with uncomplicated acute cystitis in Melbourne, Australia: prevalence, predictors and clinical impact.

Background: Australian guidelines recommend trimethoprim or nitrofurantoin as first-line agents for uncomplicated urinary tract infections (UTIs). Laboratory surveillance indicates high rates of trimethoprim resistance among urinary bacterial isolates, but there are scant local clinical data about risk factors and impact of trimethoprim resistance. Objectives: To determine the prevalence, risk factors, mechanism and impact of resistance to first-line antibiotic therapy for uncomplicated UTIs in the community setting. Methods: A prospective observational study from October 2019 to November 2021 in four general practices in Melbourne, Australia. Female adult patients prescribed an antibiotic for suspected or confirmed uncomplicated acute cystitis were eligible. Primary outcome was urine isolates with resistance to trimethoprim and/or nitrofurantoin. Results: We recruited 87 participants across 102 UTI episodes with median (IQR) age of 63 (47-76) years. Escherichia coli was the most common uropathogen cultured (48/62; 77%); 27% (13/48) were resistant to trimethoprim (mediated by a dfrA gene) and none were resistant to nitrofurantoin. Isolates with resistance to a first-line therapy were more common among patients reporting a history of recurrent UTIs [risk ratio (RR): 2.08 (95% CI: 1.24-3.51)] and antibiotic use in the previous 6 months [RR: 1.89 (95% CI: 1.36-2.62)]. Uropathogen resistance to empirical therapy was not associated with worse clinical outcomes. Conclusions: Resistance to trimethoprim is common in uncomplicated UTIs in Australia but may not impact clinical outcomes. Further research is warranted on the appropriateness of trimethoprim as empirical therapy, particularly for patients with antimicrobial resistance risk factors.

Coronary Stenosis and Cardiogenic Shock Secondary to Aortitis Following Aortic Root Support Procedure.

A woman with recent personalized external aortic root support implant presented in cardiogenic shock with bilateral coronary ostial occlusion and aortic inflammation requiring emergency coronary angioplasty. Subsequent computed tomography with positron emission tomography scanning demonstrated aortitis with extensive inflammation adjacent to the personalized external aortic root support mesh, the first report of this important complication.

Priority populations' experiences of isolation, quarantine and distancing for COVID-19: protocol for a longitudinal cohort study (Optimise Study).

INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.

Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5' untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.

Building a safety culture for infection prevention and control adherence at Howard Springs: A workplace survey.

BACKGROUND: Building a safety culture is essential to facilitate infection prevention and control (IPC) adherence in workplaces. We aimed to explore perceptions, barriers and facilitators to IPC procedures by the Australian Medical Assistance Team (AUSMAT) at Howard Springs International Quarantine Facility (HSIQF). METHODS: We performed a descriptive analysis of a cross-sectional survey administered to the AUSMAT employed at HSQIF from October 2020 to April 2021. We described motivation, training and compliance to IPC adherence and Likert scales described the level of agreement to the success of IPC procedures across the domains of communication, risk, trust, safety and environment, from the individual, team and organisational perspective. RESULTS: There were 101 participants (response rate 59%, 101/170) and 70% (71/101) were clinical. There was strong agreement to the success of IPC procedures, with a median 4 (agree) or 5 (strongly agree) across each domain and perspective of the 67 Likert items. Clinical staff reported slightly higher agreement than non-clinical staff across Likert items. To improve IPC compliance, most reported that daily training should be provided (77/97, 79%) and daily training was very or extremely effective (91/97, 93%). Participants were motivated by protecting self, friends, family and the community rather than workplace pressures. Barriers to IPC compliance were the ambient environment and fatigue. CONCLUSIONS: A safety culture was successfully built at HSQIF to optimise IPC adherence whilst managing multiple hazards including prevention of COVID-19 transmission. Strategies implemented by AUSMAT at the quarantine facility may inform the development of safety culture in other settings.

Future Prediction of Close Contacts in IoT-based Contact Tracing System using a New Real-Life Dataset.

Contact tracing is an effective method for mitigating the infectious diseases spread and it played a crucial role in reducing COVID-19 outbreak. Since the pandemic, there has been an increased concern regarding people's health in hospital and office settings, as these limited air exchange spaces provide a conductive medium for virus spread. Various technologies were used to recognize close contacts autonomously, in addition, multiple machine learning attempts were carried out to determine proximity in contact tracing. This study, however, proposes a unique concept in contact tracing: forecasting future close contact prior to occurrence in order to regulate and control it rather than tracking past occurrences. For our research, we constructed a completely new real-life dataset that was collected during the pandemic in a hospital infectious ward (Alfred Hospital, Melbourne, Australia) utilizing a Bluetooth Low Energy (BLE) Internet of Things (IoT) system. Our prediction technique considers two types of environments: single transceiver environments and multiple transceivers settings, these transceivers record the nearby tags' BLE received signal strength indicator (RSSI) values. The system employs mathematical models and supervised machine learning (ML) algorithms to solve regression and classification problems for workers' pattern recognition within the environment. The output is compared using different metrics, such as efficiency, which reached more than 80%, root mean square errors and mean absolute errors which were as low as 2.4 and 1.2 respectively in some models.

Telehealth for Comprehensive Care to Quarantine Residents: A Novel Approach and Lessons Learned.

Proactive engagement and care with regular and timely information are required to manage the health and well-being of people in quarantine. At Australia's Howard Springs International Quarantine Facility, a telehealth model was rapidly established using trained non-clinical Customer Service Officers (CSO's) with the aim to provide comprehensive care to residents, maximize staff safety, and reduce clinical workforce capacity pressures. We describe this model, whereby CSO's provided residents with daily COVID-19 symptom and well-being screening, weekly psychological screening, and ongoing linkage to additional clinical and administrative services. In addition, CSO's went beyond these duties to deliver personalized care through delivery of care packages and attendance of the departure point to farewell residents. From October 2020 to May 2021, across 7105 residents, we estimated that CSO's prevented over 75 000 face-to-face resident visits, which reduced workforce requirements and preserved staff safety through minimizing potential COVID-19 transmission and time spent in personal protective equipment in the challenging ambient environment. We share key lessons learned which may inform future telehealth models and guide a positive experience for quarantine residents.

The incidence of nosocomial bloodstream infection and urinary tract infection in Australian hospitals before and during the COVID-19 pandemic: an interrupted time series study.

BACKGROUND: The COVID-19 pandemic has had a significant impact on healthcare including increased awareness of infection prevention and control (IPC). The aim of this study was to explore if the heightened awareness of IPC measures implemented in response to the pandemic influenced the rates of healthcare associated infections (HAI) using positive bloodstream and urine cultures as a proxy measure. METHODS: A 3 year retrospective review of laboratory data from 5 hospitals (4 acute public, 1 private) from two states in Australia was undertaken. Monthly positive bloodstream culture data and urinary culture data were collected from January 2017 to March 2021. Occupied bed days (OBDs) were used to generate monthly HAI incidence per 10,000 OBDs. An interrupted time series analysis was undertaken to compare incidence pre and post February 2020 (the pre COVID-19 cohort and the COVID-19 cohort respectively). A HAI was assumed if positive cultures were obtained 48 h after admission and met other criteria. RESULTS: A total of 1,988 bloodstream and 7,697 urine positive cultures were identified. The unadjusted incident rate was 25.5 /10,000 OBDs in the pre-COVID-19 cohort, and 25.1/10,000 OBDs in the COVID-19 cohort. The overall rate of HAI aggregated for all sites did not differ significantly between the two periods. The two hospitals in one state which experienced an earlier and larger outbreak demonstrated a significant downward trend in the COVID-19 cohort (p = 0.011). CONCLUSION: These mixed findings reflect the uncertainty of the effect the pandemic has had on HAI's. Factors to consider in this analysis include local epidemiology, differences between public and private sector facilities, changes in patient populations and profiles between hospitals, and timing of enhanced IPC interventions. Future studies which factor in these differences may provide further insight on the effect of COVID-19 on HAIs.

HDAC3 is critical in tumor development and therapeutic resistance in Kras-mutant non-small cell lung cancer.

HDAC3 is one of the main targets of histone deacetylase (HDAC) inhibitors in clinical development as cancer therapies, yet the in vivo role of HDAC3 in solid tumors is unknown. We identified a critical role for HDAC3 in Kras-mutant lung cancer. Using genetically engineered mouse models (GEMMs), we found that HDAC3 is required for lung tumor growth in vivo. HDAC3 was found to direct and enhance the transcription effects of the lung cancer lineage transcription factor NKX2-1 to mediate expression of a common set of target genes. We identified FGFR1 as a critical previously unidentified target of HDAC3. Leveraging this, we identified that an HDAC3-dependent transcriptional cassette becomes hyperactivated as Kras/LKB1-mutant cells develop resistance to the MEK inhibitor trametinib, and this can be reversed by treatment with the HDAC1/HDAC3 inhibitor entinostat. We found that the combination of entinostat plus trametinib treatment elicits therapeutic benefit in the Kras/LKB1 GEMM.

Transthoracic Echocardiographic Assessment of the Heart in Pregnancy-a position statement on behalf of the British Society of Echocardiography and the United Kingdom Maternal Cardiology Society.

Pregnancy is a dynamic process associated with profound hormonally mediated haemodynamic changes which result in structural and functional adaptations in the cardiovascular system. An understanding of the myocardial adaptations is important for echocardiographers and clinicians undertaking or interpreting echocardiograms on pregnant and post-partum women. This guideline, on behalf of the British Society of Echocardiography and United Kingdom Maternal Cardiology Society, reviews the expected echocardiographic findings in normal pregnancy and in different cardiac disease states, as well as echocardiographic signs of decompensation. It aims to lay out a structure for echocardiographic scanning and surveillance during and after pregnancy as well as suggesting practical advice on scanning pregnant women.

Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1.

Cells respond to mitochondrial poisons with rapid activation of the adenosine monophosphate-activated protein kinase (AMPK), causing acute metabolic changes through phosphorylation and prolonged adaptation of metabolism through transcriptional effects. Transcription factor EB (TFEB) is a major effector of AMPK that increases expression of lysosome genes in response to energetic stress, but how AMPK activates TFEB remains unresolved. We demonstrate that AMPK directly phosphorylates five conserved serine residues in folliculin-interacting protein 1 (FNIP1), suppressing the function of the folliculin (FLCN)-FNIP1 complex. FNIP1 phosphorylation is required for AMPK to induce nuclear translocation of TFEB and TFEB-dependent increases of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and estrogen-related receptor alpha (ERRα) messenger RNAs. Thus, mitochondrial damage triggers AMPK-FNIP1-dependent nuclear translocation of TFEB, inducing sequential waves of lysosomal and mitochondrial biogenesis.

Prevalence of pre-eclampsia and adverse pregnancy outcomes in women with pre-existing cardiomyopathy: a multi-centre retrospective cohort study.

Pre-eclampsia is associated with postnatal cardiac dysfunction; however, the nature of this relationship remains uncertain. This multicentre retrospective cohort study aimed to determine the prevalence of pre-eclampsia in women with pre-existing cardiac dysfunction (left ventricular ejection fraction < 55%) and explore the relationship between pregnancy outcome and pre-pregnancy cardiac phenotype. In this cohort of 282 pregnancies, pre-eclampsia prevalence was not significantly increased (4.6% [95% C.I 2.2-7.0%] vs. population prevalence of 4.6% [95% C.I. 2.7-8.2], p = 0.99); 12/13 women had concurrent obstetric/medical risk factors for pre-eclampsia. The prevalence of preterm pre-eclampsia (< 37 weeks) and fetal growth restriction (FGR) was increased (1.8% vs. 0.7%, p = 0.03; 15.2% vs. 5.5%, p < 0.001, respectively). Neither systolic nor diastolic function correlated with pregnancy outcome. Antenatal ß blockers (n = 116) were associated with lower birthweight Z score (adjusted difference - 0.31 [95% C.I. - 0.61 to - 0.01], p = 0.04). To conclude, this study demonstrated a modest increase in preterm pre-eclampsia and significant increase in FGR in women with pre-existing cardiac dysfunction. Our results do not necessarily support a causal relationship between cardiac dysfunction and pre-eclampsia, especially given the population's background risk status. The mechanism underpinning the relationship between cardiac dysfunction and FGR merits further research but could be influenced by concomitant ß blocker use.

Aortopathy in pregnancy.

Aortic dissection is one of the most common causes of death in pregnancy. Most cases are caused by hereditary thoracic aortopathy (HTA), and women are often unaware they are at risk. Awareness, early recognition and involvement of senior clinicians from the expert cardio-obstetric team are essential to facilitate early diagnosis and carefully planned and coordinated antenatal and postnatal care. Frequent imaging antenatally and good blood pressure control are key. Delivery needs particular attention with optimal pain control and techniques to minimise maternal effort. Dissection is most common post partum and a period of close surveillance with meticulous blood pressure control after delivery is crucial, as well as follow-up of the baby in paediatric services. All women with a family history of aortic dissection or sudden death should be investigated. Women with known HTA should be offered specialist individualised pre-pregnancy counselling, including advice about genetics and inheritance, before starting a family. Future research is directed towards more individualised risk assessment, pre-pregnancy advice and pharmacological options to reduce dissection risk.

An outdoor hotel quarantine facility model in Australia: best practice with optimal outcomes.

OBJECTIVE: To describe the operationalisation of a novel outdoor quarantine facility managed by the Australian Medical Assistance Team, the Howard Springs International Quarantine Facility (HSIQF) at the Centre for National Resilience in the Northern Territory, Australia. METHODS: We collated documentation and data from HSIQF to describe policies and procedures implemented and performed a descriptive analysis of key procedures and outcomes. RESULTS: From 23 October 2020 to 31 March 2021, 2.2% (129/5,987) of residents were confirmed COVD-19 cases. On average per day, 82 [Interquartile Range (IQR): 29-95] staff completed personal protective equipment (PPE) training, 94 [IQR: 90-104] staff completed antigen testing and 51 [IQR: 32-136] staff completed polymerase chain reaction testing. The operation focused on building a safe environment with infection prevention and control adherence and workforce sustainability. There was no leakage of SARS-CoV-2 to staff or the community and no PPE compromises requiring staff to quarantine for 14 days. CONCLUSION: HSIQF demonstrates the operationalisation of an effective, safe and replicable quarantine system. IMPLICATIONS FOR PUBLIC HEALTH: Quarantine is a critical public health tool for pandemic control. The HSIQF operations may be useful to inform the establishment and management of quarantine facilities for future and current disease outbreaks.

Electronic monitoring of doffing using video surveillance to minimise error rate and increase safety at Howard Springs International Quarantine Facility.

BACKGROUND: Safe donning and doffing of personal protective equipment (PPE) are critical to prevent transmission of infectious diseases. Novel strategies to improve infection prevention and control (IPC) adherence can optimise safety. We describe and quantify video surveillance of doffing at an outdoor hotel quarantine facility led by the Australian Medical Assistance Team in the Northern Territory, Australia. METHODS: Motion-activated video cameras were installed in seven areas where personnel doffed PPE upon exit from an area dedicated to quarantined residents. Video footage was reviewed daily and compliance issues were identified using a standardised checklist and risk graded to initiate feedback. We collated audit data from 1 February to 18 April 2021 to describe trends by month, staff group, doffing component and risk. RESULTS: In 235 h of video footage, 364 compliance issues were identified, of which none were considered high-risk compromising to PPE integrity. Compliance issues were low risk (55/364, 15%) or moderate risk (309/364, 85%) and the most common issue was missed or inadequate hand hygiene (156/364, 43%). Compliance issues per minute of video footage reviewed decreased following introduction of the activity, from 24 per 1000 in February to 7 per 1000 in March and April. CONCLUSION: Video surveillance with feedback supported rapid response to improve IPC adherence in a challenging ambient environment. The activity focused on perfection to identify compliance issues that would go unreported in most healthcare settings and contributed to a suit of activities that prevented any high-risk PPE breaches or compromises to safety.